Hearing impairment is the most prevalent sensory deficit of human beings, and are said to occur in at least one of ten persons. Hearing impairment can be caused by a variety of factors including ototoxic substances such as aminoglicoside antibiotics or cisplatin (CDDP), noise and ageing.
These factors affect the inner ear hair cells in the organ of Corti which function as sensory cells that collect and transfer auditory signals to the brain via the auditory neurons. Moreover, degeneration of the auditory nerve occurs secondary to the loss of the sensory hair cells, thus exacerbating the functional impairment of hearing.
In general, hair cells and auditory neurons in mammalian vertebrates have no capacity for postembryonic cellular mitosis to generate new hair cells and neurons. In the mammalian stato-acoustic epithelia, a low level of regeneration is possible for the vestibular receptors in vivo. However, no regeneration of auditory sensory epithelium was observed in vivo, except a very restricted regeneration observed in neonatal mouse cochlear in vitro.
For the treatment of severely deaf ears, the cochlear implant has provided great benefits to patients and has been shown to provide an effective intervention. However, the benefit of cochlear prosthesis depends on the quality and quantity of the auditory nerve population, and their loss severely compromises the hearing benefits it provides.
The past studies show a clear relationship between the total number of viable auditory neurons available for stimulation and the performance of subjects receiving cochlear implants. This shows that the implant cannot always produce satisfactory results.
It is therefore necessary to develop the therapeutic strategy of preserving or regenerating the auditory neurons to increase the effectiveness of the implant. Recent studies revealed that multiple neurotrophic factors such as nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), neurotrophic factor-3 or NT-4/5 have been shown to have effects on the survival of inner ear auditory neurons, including spiral ganglion cells (SGCs).
A prior art relevant to the present invention, that is, U.S. Pat. No. 6,136,785 discloses a method of protecting sensory hair cells in the inner ear against damage caused by ototoxic substances such as aminoglicoside, which comprises administering a growth factor or a mixture thereof into a vertebrate. As its relevant prior arts, WO-A 98/00014, U.S. Pat. No. 6,017,886, JP-A 2002-503687 etc. are also known.